Is Memantine Effective in Mild Alzheimer Disease?
Schneider LS, Dagerman KS, Higgins JPT, McShane R
Arch Neurol. 2011 Apr 11. [Epub ahead of print]
In the United States and Europe, memantine is approved for treatment of moderate to severe Alzheimer disease (AD), on the basis of Mini-Mental State Examination (MMSE) scores. However, memantine is often prescribed off-label in mild AD and even in mild cognitive impairment; this use is supported in part by a manufacturer-sponsored meta-analysis suggesting that memantine is effective in mild AD.
The goal of this study was to evaluate the efficacy of memantine in mild AD by directly analyzing evidence from clinical trials. To identify randomized, placebo-controlled, parallel-group clinical trials of memantine in patients with mild to moderate AD, Schneider and coworkers systematically searched manufacturer-sponsored meta-analyses, registries, presentations, and published articles. One reviewer extracted data on characteristics and outcomes from these trials; the data were confirmed by a second reviewer. Using fixed-effects models, meta-analyses were conducted as inverse variance-weighted averages of mean differences.
Three eligible trials enrolled a total of 431 patients with mild AD (MMSE scores 20-23) and 697 patients with moderate AD (MMSE scores 10-19). For patients with mild AD, outcomes in the memantine group did not differ significantly from those in the placebo, within any trial or in a meta-analysis of pooled data. Specifically, there were no significant differences on the Alzheimer Disease Assessment Scale-cognitive subscale (ADAS-cog), the Clinician's Interview-Based Impression of Change plus caregiver's input (CIBIC-plus), the Alzheimer Disease Cooperative Study-activities of daily living (ADCS-ADL) scale, or the Neuropsychiatric Inventory (NPI).
Memantine was associated with small differences from placebo in patients with moderate AD on the ADAS-cog (-1.33 [95% CI, -2.28 to -0.38]) and the CIBIC-plus (-0.16 [95% CI, -0.32 to 0.00]) but not on the ADCS-ADL scale or the NPI.
Lack of Evidence for the Efficacy of Memantine in Mild Alzheimer Disease
Schneider LS, Dagerman KS, Higgins JPT, McShane R
Arch Neurol. 2011 Apr 11. [Epub ahead of print]
Study Summary
In the United States and Europe, memantine is approved for treatment of moderate to severe Alzheimer disease (AD), on the basis of Mini-Mental State Examination (MMSE) scores. However, memantine is often prescribed off-label in mild AD and even in mild cognitive impairment; this use is supported in part by a manufacturer-sponsored meta-analysis suggesting that memantine is effective in mild AD.
The goal of this study was to evaluate the efficacy of memantine in mild AD by directly analyzing evidence from clinical trials. To identify randomized, placebo-controlled, parallel-group clinical trials of memantine in patients with mild to moderate AD, Schneider and coworkers systematically searched manufacturer-sponsored meta-analyses, registries, presentations, and published articles. One reviewer extracted data on characteristics and outcomes from these trials; the data were confirmed by a second reviewer. Using fixed-effects models, meta-analyses were conducted as inverse variance-weighted averages of mean differences.
Three eligible trials enrolled a total of 431 patients with mild AD (MMSE scores 20-23) and 697 patients with moderate AD (MMSE scores 10-19). For patients with mild AD, outcomes in the memantine group did not differ significantly from those in the placebo, within any trial or in a meta-analysis of pooled data. Specifically, there were no significant differences on the Alzheimer Disease Assessment Scale-cognitive subscale (ADAS-cog), the Clinician's Interview-Based Impression of Change plus caregiver's input (CIBIC-plus), the Alzheimer Disease Cooperative Study-activities of daily living (ADCS-ADL) scale, or the Neuropsychiatric Inventory (NPI).
Memantine was associated with small differences from placebo in patients with moderate AD on the ADAS-cog (-1.33 [95% CI, -2.28 to -0.38]) and the CIBIC-plus (-0.16 [95% CI, -0.32 to 0.00]) but not on the ADCS-ADL scale or the NPI.
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